This Core Grant support is for administration, Senior Staff salaries, central office, glassware washing and animal facility personnel, central GCDC operation functions, tissue culture media preparation, electron microscopy and histopathology central functions, tumor cells procurement and characterization unit, synthetic chemistry central resource, shared instrument, biomathematical resource, development of new laboratory units and temporary support of programs. The scientific functions of the GCDC are related to: 1) the development and study of new drugs originating in the medicinal chemistry groups of the Center or obtained from the outside; 2) the study of basic aspects of cell metabolism and biology that may lead to the development of new compounds and treatments, with emphasis on (a) regulation of normal and neoplastic cell metabolism (b) alterations leading to neoplastic processes and cell transformation, (c) role of the plasma membrane, and (d) selectivity of immunomodulation by drugs and tumors; 3) the preclinical study of the biochemical and pharmacological basis for the selectivity of anticancer drugs and treatments, with emphasis on the acquisition and integration of information leading towards the identification of means to increase the selectivity of drug action against tumors; 4) the study of the molecular and pharmacological basis of natural and acquired resistance to drugs and treatments and their expression in heterogeneous tumor cell populations; 5) the study, in close cooperation with clinical departments, of the pharmacological and biochemical determinants of drug action in humans with emphasis on (a) development of new drugs, (b) clarification of the mode of action of known drugs, (c) development of new treatments through the identification of the pharmacological and biochemical determinants of tumor sensitivity in individual patients, and (d) determinantion of biochemical characteristics of different types of cancer or of different stages of diseases.